Abstract

Dysfunctions of glomerular podocytes and triggering of apoptotic processes in them are the main molecular causes of diabetic nephropathy and other kidney diseases. Pathogenetic factors causing these dysfunctions of podocytes are hyperglycemia, increased levels of advanced glycation end-products, oxidative stress, increased activity of inflammatory factors, and endoplasmic reticulum stress. These factors and their combinations result in the triggering of a number of intracellular signaling pathways that cause activation of apoptosis and reduce the survival of podocytes. Among these pathways are: (1) the Wnt/β-catenin pathway, which is activated by the Wnt-proteins when they bind to the complex of Frizzled receptors and LRP co-receptors; (2) the mTOR-dependent signaling pathway, including the mTORC1 and mTORC2 complexes, which are involved in the regulation of autophagy and endoplasmic reticulum stress and are regulated by various stimuli and effectors, in particular, the AMP-activated protein kinase; (3) the Rho/ROCK signaling pathway, including GTPases of the Rho family and Rho-associated protein kinase ROCK1; (4) calcium-dependent signaling pathways triggered by an increase in the concentration of intracellular Ca²⁺, primarily through the activation of calcium channels of the TRPC family. The review provides a detailed analysis of the current state of knowledge about the molecular mechanisms responsible for the regulation of apoptotic processes in glomerular podocytes and also considers hormonal and other factors that regulate them both under normal conditions and under the conditions of lesions induced by hyperglycemia and diabetic nephropathy.

中文翻译：

---

糖尿病肾病肾小球足细胞凋亡的分子机制

摘要

肾小球足细胞的功能障碍和凋亡过程的触发是糖尿病性肾病和其他肾脏疾病的主要分子原因。导致足细胞功能异常的致病因素是高血糖症，晚期糖基化终产物水平增加，氧化应激，炎症因子活性增加以及内质网应激。这些因素及其组合导致许多细胞内信号通路的触发，这些信号通路引起细胞凋亡的激活并降低足细胞的存活。这些途径包括：（1）Wnt /β-catenin途径，当Wnt蛋白与卷曲蛋白受体和LRP共受体的复合物结合时，被Wnt蛋白激活。（2）mTOR依赖性信号传导途径，包括mTORC1和mTORC2复合物，它们参与自噬和内质网应激的调节，并受到各种刺激和效应物，特别是AMP激活的蛋白激酶的调节；（3）Rho / ROCK信号传导途径，包括Rho家族的GTP酶和Rho相关蛋白激酶ROCK1；（4）细胞内Ca浓度增加触发的钙依赖性信号通路²⁺，主要是通过激活TRPC家族的钙通道。该综述提供了有关负责调节肾小球足细胞凋亡过程的分子机制的当前知识状态的详细分析，还考虑了在正常情况下以及在高血糖和高血糖引起的病变情况下调节它们的激素和其他因素。糖尿病肾病。